In order to test hypothesis three the expenditures associated with the first neutropenia hospitalization within the first, third and sixth month after the start of chemotherapy were examined. The trends in magnitude were very similar to the findings from length of stay, which further
emphasizes the fact that length of stay is one of the chief determinants of Medicare costs associated with a hospitalization (Lyman, 2004). None of the effects were statistically significant, probably because of the small sample size of women who get hospitalized, hence the first part of the hypothesis three could not be corroborated as well. The effect of duration of primary prophylactic G-CSF
administration on neutropenia hospitalization expenditures could not be assessed due to the small sample size of the women receiving any primary prophylactic G-CSF as well as getting hospitalized.
The second part of hypothesis three looks at the effect of primary prophylactic G-CSF on overall Medicare Expenditures for one year after the start of chemotherapy. The initial aim was to see if primary prophylactic G-CSF administration prevented early recurrence and other worse outcomes, and hence lowered the cost of breast cancer management and treatment in the first year after the start of chemotherapy. The study, however, found reverse trends. Women who received primary
prophylactic G-CSF had higher mean overall expenditure and this effect was statistically significant. In the post-matching analysis the overall expenditures were 57.25% higher in women receiving primary prophylactic G-CSF (Table 11). Women receiving a higher duration of primary prophylactic G-CSF also had higher overall Medicare expenditure during the first year after start of chemotherapy. Receiving 5 or more days of primary prophylactic G-CSF increased the overall expenditure by 19.62%, and increase in primary prophylactic G-CSF by one day increased the overall expenditure by 1.74% (Table 12).
There could be multiple reasons for higher overall expenditure in spite of effective primary prophylaxis. The administration of primary prophylactic G-CSF increased the successful
administration of the first course of chemotherapy and radiation therapy (as discussed in the next section). Since the bulk of these therapies are administered in the first year, increased adherence to these therapies will increase the Medicare expenditure in the first year. It is also important to
understand that G-CSF is expensive, and the costs for prophylactic G-CSF administration during the entire first course chemotherapy could range between $5,000 to $30,000. This considerable cost could offset cost reductions due to reduced neutropenia management and hospitalization costs. In order to understand the main driving factors behind higher first year expenditure in women receiving primary prophylactic G-CSF a descriptive analysis was performed to identify different components of these overall costs (Table 14).
In the matched data the average G-CSF expenditure in the first year for women who received the drug as primary prophylaxis was $7914 versus $1369 for women who did not receive the drug as primary prophylaxis (but received it later). The maximum expenditure of G-CSF for women who received primary prophylaxis was $44204 and was below $20,000 for 95% of the women receiving primary prophylaxis. On the other hand the expenditure was below $8,000 for 95% of the women not having received primary prophylaxis, with the maximum expenditure being $24927. Seventy percent of women who did not receive primary prophylactic G-CSF had no G-CSF expenditure in the first year.
Chemotherapy expenditures were twice as high for women receiving primary prophylactic G- CSF. Fifty percent of women who did not receive primary prophylaxis had less than $4,000 of chemotherapy expenses in the first year, and 50% of the women having received G-CSF had more than $10,000 of chemotherapy expenses in the first year with a maximum of $61,705. Given both the difference in the expenditure due to G-CSF and chemotherapy, it is not surprising that women having received primary prophylactic G-CSF have high expenditures in the first year in spite of any cost reductions due to reduced neutropenia management and hospitalization costs. It is also important to note that in women receiving primary prophylactic G-CSF, G-CSF accounts for nearly 30% of the overall costs in the first year and is almost as big a contributor to overall costs as chemotherapy (at 40%).
Previous studies predominantly look at neutropenia hospitalization and immediate care costs and have ambiguous findings in terms of the cost reduction due to G-CSF. These past studies are broadly of three types - some directly estimate the expenditures associated with neutropenia hospitalization; some develop cost models to estimate the threshold above which prophylaxis of neutropenia becomes cost-effective; and some estimate the reduction in hospitalization costs and other neutropenia related costs due to G-CSF administration.
Studies that just look at the cost of neutropenia hospitalization have found that cost of care and inpatient care is around 1.5 to 2 times higher in women experiencing neutropenia (Weycker, 2006; Gandhi, 2001) and the neutropenia hospitalization cost could range from $10,000 to $30,000 (Eldar-Lissai, 2007; Kuderer, 2006; Weycker, 2007; Weycker 2006; Brooks, 2003). Studies also find that the cost of care for neutropenia predominantly depends on the patient’s baseline clinical status like cancer stage and existence of other comorbidities (Chrischilles, 2005).
Studies looking at cost-effectiveness of G-CSF using cost-models have demonstrated that primary prophylactic G-CSF is cost-reducing and cost effective in patients with high risk of developing neutropenia, febrile neutropenia or neutropenia hospitalization (>20% risk according to the currently accepted model by ASCO) (Eldar-Lissai, 2007; Uyl-de Groot, 1996; Lyman 2004; Lyman, 1993). Uyl-de Groot and colleagues show that G-CSF is cost effective in terms of reducing hospitalization and antibiotic administration costs in patients receiving chemotherapy, especially for patients with higher risk of infections (Uyl-de Groot, 1996). These cost-effectiveness models only include direct healthcare costs and do not include out-of-pocket costs, indirect costs (due to
caregiver’s time and any other form of loss of pay), intangible costs and quality of life considerations. Lyman and colleagues suggest that prophylactic G-CSF should be administered even if the risk is less than 20% in patients with possibly complicated or prolonged course of management such as the elderly patients (Lyman, 1998).
Studies looking at reductions in costs due to neutropenia are mostly clinical trials and retrospective chart reviews with low external validity (Glaspy, 1993; Zagonel, 1994; Dranitsaris, 1995; Bassan, 1997). These studies have mixed findings. Some studies reveal a drop in costs, on average, in patients receiving primary prophylactic G-CSF compared to those not receiving the prophylaxis (Glaspy, 1993; Zagonel, 1994), while some reveal no change in costs (Dranitsaris, 1995;
Bassan, 1997). Two studies found that although the neutropenia hospitalization length of stay was reduced in patients receiving G-CSF, the cost reduction was offset by the initial cost of G-CSF administration (Dranitsaris, 1995; Bassan, 1997).